Dong Xue-Man, Chen Lin, Xu Yu-Xin, Wu Pu, Xie Tian, Liu Zhao-Qian
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
School of Pharmacy, Hangzhou Normal University, Hangzhou, China.
Cancer Gene Ther. 2025 Feb;32(2):165-183. doi: 10.1038/s41417-024-00858-5. Epub 2025 Jan 10.
Esophageal cancer (EC) is one of the most common malignancies worldwide with the character of poor prognosis and high mortality. Despite significant advancements have been achieved in elucidating the molecular mechanisms of EC, for example, in the discovery of new biomarkers and metabolic pathways, effective treatment options for patients with advanced EC are still limited. Metabolic heterogeneity in EC is a critical factor contributing to poor clinical outcomes. This heterogeneity arises from the complex interplay between the tumor microenvironment and genetic factors of tumor cells, which drives significant metabolic alterations in EC, a process known as metabolic reprogramming. Understanding the mechanisms of metabolic reprogramming is essential for developing new antitumor therapies and improving treatment outcomes. Targeting the distinct metabolic alterations in EC could enable more precise and effective therapies. In this review, we explore the complex metabolic changes in glucose, amino acid, and nucleotide metabolism during the progression of EC, and how these changes drive unique nutritional demands in cancer cells. We also evaluate potential therapies targeting key metabolic enzymes and their clinical applicability. Our work will contribute to enhancing knowledge of metabolic reprogramming in EC and provide new insights and approaches for the clinical treatment of EC.
食管癌(EC)是全球最常见的恶性肿瘤之一,具有预后差和死亡率高的特点。尽管在阐明食管癌的分子机制方面取得了重大进展,例如发现了新的生物标志物和代谢途径,但晚期食管癌患者的有效治疗选择仍然有限。食管癌中的代谢异质性是导致临床预后不良的关键因素。这种异质性源于肿瘤微环境与肿瘤细胞遗传因素之间的复杂相互作用,这在食管癌中驱动了显著的代谢改变,这一过程称为代谢重编程。了解代谢重编程的机制对于开发新的抗肿瘤疗法和改善治疗结果至关重要。针对食管癌中独特的代谢改变可能会实现更精确有效的治疗。在这篇综述中,我们探讨了食管癌进展过程中葡萄糖、氨基酸和核苷酸代谢的复杂变化,以及这些变化如何驱动癌细胞独特的营养需求。我们还评估了针对关键代谢酶的潜在疗法及其临床适用性。我们的工作将有助于增强对食管癌代谢重编程的认识,并为食管癌的临床治疗提供新的见解和方法。